A non-randomised open-label exploratory ‘window of opportunity’ study of TG02 treatment in patients with locally advanced primary and recurrent RAS mutant colorectal cancer

A non-randomised open-label exploratory ‘window of opportunity’ study of TG02 treatment in patients with locally advanced primary and recurrent RAS mutant colorectal cancer

Background: TG02 is a peptide-based cancer vaccine eliciting immune responses to oncogenic codon 12/13 RAS mutations. This phase 1 clinical trial (NCT02933944) assessed the safety and immunological efficacy of TG02 adjuvanted by GM-CSF in patients with KRAS-mutant colorectal cancer. Methods: In the...

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Main Authors: Sara Roth, Kasmira Claire Wilson, Robert George Ramsay, Catherine Mitchell, Shienny Sampurno, Toan Duc Pham, Joseph Cherng Huei Kong, Stephen Q. Wong, Alexander Graham Heriot, Sanjeev Deva, Matthew Burge, Cecilie Sverdrup, Anne-Sophie Moller, Lukasz Kuryk, Jon Amund Eriksen, Magnus Jaderberg, John Raymond Zalcberg, Michael Michael
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Heliyon
Subjects:
Colorectal cancer
Cancer vaccine
KRAS
TG02
GM-CSF
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844024173951
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Summary:Background: TG02 is a peptide-based cancer vaccine eliciting immune responses to oncogenic codon 12/13 RAS mutations. This phase 1 clinical trial (NCT02933944) assessed the safety and immunological efficacy of TG02 adjuvanted by GM-CSF in patients with KRAS-mutant colorectal cancer. Methods: In the interval between completing CRT and pelvic exenteration, patients with resectable KRAS mutation-positive, locally advanced primary or current colorectal cancer, received 5–6 doses of TG02/GM-CSF. Immune response was defined as a positive delayed-type hypersensitivity or positive T cell proliferation assay response. Tumour biopsies were analysed for tumour-infiltrating lymphocytes (TILs) and blood for CEA and ctDNA. TILs and tumouroids were cultured, characterised and tested for their killing efficacy. Results: Six patients with rectal cancer were recruited to evaluate TG02. Three patients experienced a total of 16 treatment-related adverse events; all grade 1. Four of the 6 patients (66.7 %) had at least one vaccine-induced TG02 immune response. Flow cytometry analysis showed high proportion of PD-1-expressing TILs in 2 of 3 patient specimens’ post-treatment. A partial to near complete pathological response was reported in 4 of 6 patients. Conclusions: This study demonstrated that TG02/GM-CSF was well tolerated and induced a vaccine specific systemic immune response in the majority of patients. Low numbers limit conclusive clinical outcome reporting. High PD-1 expression on post-treatment TILs encourages the addition of an immune checkpoint inhibitor to TG02 and potentially other studies of peptide vaccines in future studies.
ISSN:2405-8440

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